Abstract
Decline in the therapeutic potential of bone marrow-derived mesenchymal stem cells (MSC) is often seen with older donors as compared to young. Although hypoxia is known as an approach to improve the therapeutic potential of MSC in term of cell proliferation and differentiation capacity, its effects on MSC from aged donors have not been well studied. To evaluate the influence of hypoxia on different age groups, MSC from young (<30 years) and aged (>60 years) donors were expanded under hypoxic (5% O2) and normal (20% O2) culture conditions. MSC from old donors exhibited a reduction in proliferation rate and differentiation potential together with the accumulation of senescence features compared to that of young donors. However, MSC cultured under hypoxic condition showed enhanced self-renewing and proliferation capacity in both age groups as compared to normal condition. Bioinformatic analysis of the gene ontology (GO) and KEGG pathway under hypoxic culture condition identified hypoxia-inducible miRNAs that were found to target transcriptional activity leading to enhanced cell proliferation, migration as well as decrease in growth arrest and apoptosis through the activation of multiple signaling pathways. Overall, differentially expressed miRNA provided additional information to describe the biological changes of young and aged MSCs expansion under hypoxic culture condition at the molecular level. Based on our findings, the therapeutic potential hierarchy of MSC according to donor’s age group and culture conditions can be categorized in the following order: young (hypoxia) > young (normoxia) > old aged (hypoxia) > old aged (normoxia).
Highlights
Mesenchymal stem cells derived from bone marrow (BM-mesenchymal stem cells (MSC)) are adult multipotent stem cells with the self-renewing capacity and the ability to differentiate into cells of various connective tissue lineages
Comparison of BM-MSC of young and aged donors under hypoxic and prolonged passage conditions MSC surface marker expressions showed that CD105, CD90 and CD44 were strongly expressed in young MSC whereas in aged MSC, the markers were present but the expression level was slightly lower
The proliferation rate of MSC remained relatively high during low passage
Summary
Mesenchymal stem cells derived from bone marrow (BM-MSCs) are adult multipotent stem cells with the self-renewing capacity and the ability to differentiate into cells of various connective tissue lineages. The acceleration of senescence was related with the decrease of cell proliferation and their life span as well as contributing to the accumulation of DNA damage leading to stem cell exhaustion (Rube et al, 2011). These marked the compromised quality of MSCs with age as well as prolonged passage under normal condition. In the case of autologous MSC transplantation for severe autoimmune diseases and old age related diseases in aged patients, the use of MSC of aged donor is still highly in demand (Wang et al, 2013; Wei et al, 2013)
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